The enzyme complex prostaglandin endoperoxide synthetase (PES) catalyzes the oxygenation of arachidonic acid (20:4) to the hydroperoxy endoperoxide PGG2 and the reduction of PGG2 to the hydroxy endoperoxide PGH2. During the reduction of PGG2 to PGH2, oxidizing agents are released which trigger the cooxygenation of a variety of xenobiotics. Among these are polycyclic aromatic hydrocarbons such as benzo(a)pyrene (BP) and 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene (BP-7,8-diol). BP-7,8-diol is cooxygenated to a diolepoxide which is believed to be the ultimate carcinogenic form of BP. We are investigating the mechanism of BP-7,8-diol cooxygenation, its occurrence in various tissues of mice and rats, and the enzymes involved. These studies will help to define the role of PES in xenobiotic metabolism and the extent to which it occurs in vivo.